Cross-talk between NR4A orphan nuclear receptors and β-catenin signaling pathway in osteoblasts

Rajalin, Ann-Marie; Aarnisalo, Piia

doi:10.1016/j.abb.2011.02.018

Cited by 27 publications

(28 citation statements)

References 55 publications

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“…Nurr1 inhibits Wnt signaling by blocking β-catenin transactivation in both 293F and MC3TC-E1 osteoblastic cells. A similar observation was made in U2OS osteosarcoma cells in which the NR4A receptors block the transcriptional activity of β-catenin through a mechanism involving the DNA-binding domain of the NR4A receptors [150]. In addition, Nur77 promotes β-catenin degradation in the cytoplasm and inhibits tumor formation in vivo through transcriptional inhibition of the Wnt pathway [8, 151].…”

Section: Nr4a Wnt and β-Cateninmentioning

confidence: 55%

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The interplay of NR4A receptors and the oncogene–tumor suppressor networks in cancer

Beard

Tenga

Chen

2015

Cellular Signalling

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Nuclear receptor (NR) subfamily 4 group A (NR4A) is a family of three highly homologous orphan nuclear receptors that have multiple physiological and pathological roles, including some in cancer. These NRs are reportedly dysregulated in multiple cancer types, with many studies demonstrating pro-oncogenic roles for NR4A1 (Nur77) and NR4A2 (Nurr1). Additionally, NR4A1 and NR4A3 (Nor-1) are described as tumor suppressors in leukemia. The dysregulation and functions of the NR4A members are due to many factors, including transcriptional regulation, protein-protein interactions, and post-translational modifications. These various levels of intracellular regulation result from the signaling cross-talk of the NR4A members with various signaling pathways, many of which are relevant to cancer and likely explain the family members' functions in oncogenesis and tumor suppression. In this review, we discuss the multiple functions of the NR4A receptors in cancer and summarize a growing body of scientific literature that describes the interconnectedness of the NR4A receptors with various oncogene and tumor suppressor pathways.

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Section: Nr4a Wnt and β-Cateninmentioning

confidence: 55%

“…Nuclear receptors, including the NR4A receptors, modulate the Wnt pathway [149, 150]. Nurr1 inhibits Wnt signaling by blocking β-catenin transactivation in both 293F and MC3TC-E1 osteoblastic cells.…”

Section: Nr4a Wnt and β-Cateninmentioning

confidence: 99%

The interplay of NR4A receptors and the oncogene–tumor suppressor networks in cancer

Beard

Tenga

Chen

2015

Cellular Signalling

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“…1B). In particular, the expression of WNT receptor FZD6 [57], beta-catenin interactor NR4A orphan nuclear receptors (NR4A1 and NR4A2) [58], and WNT target genes as CCND1 (cyclin D1) and SPRY4 were increased in ATP-treated cells. Consistently, some WNT/b -catenin signaling pathway inhibitors, such as DKK2 [59], SFRP1 [60], and SFRP4 [61], were downregulated (Fig.…”

Section: Gene Expression Profile Of Atp-treated Undifferentiated Bm-hmentioning

confidence: 96%

Extracellular Purines Promote the Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells to the Osteogenic and Adipogenic Lineages

Ciciarello

Zini

Rossi

et al. 2013

Stem Cells and Development

101

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Extracellular nucleotides are potent signaling molecules mediating cell-specific biological functions, mostly within the processes of tissue damage and repair and flogosis. We previously demonstrated that adenosine 5¢-triphosphate (ATP) inhibits the proliferation of human bone marrow-derived mesenchymal stem cells (BMhMSCs), while stimulating, in vitro and in vivo, their migration. Here, we investigated the effects of ATP on BM-hMSC differentiation capacity. Molecular analysis showed that ATP treatment modulated the expression of several genes governing adipogenic and osteoblastic (ie, WNT-pathway-related genes) differentiation of MSCs. Functional studies demonstrated that ATP, under specific culture conditions, stimulated adipogenesis by significantly increasing the lipid accumulation and the expression levels of the adipogenic master gene PPARc (peroxisome proliferator-activated receptor-gamma). In addition, ATP stimulated osteogenic differentiation by promoting mineralization and expression of the osteoblast-related gene RUNX2 (runt-related transcription factor 2). Furthermore, we demonstrated that ATP stimulated adipogenesis via its triphosphate form, while osteogenic differentiation was induced by the nucleoside adenosine, resulting from ATP degradation induced by CD39 and CD73 ectonucleotidases expressed on the MSC membrane. The pharmacological profile of P2 purinergic receptors (P2Rs) suggests that adipogenic differentiation is mainly mediated by the engagement of P2Y1 and P2Y4 receptors, while stimulation of the P1R adenosine-specific subtype A2B is involved in adenosine-induced osteogenic differentiation. Thus, we provide new insights into molecular regulation of MSC differentiation.

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“…TR3 can activate Wnt signalling by transrepression of the Wnt signalling antagonists DACT1 and CITED1 in melanoma cells 31. In contrast, an inhibitory effect of TR3 on Wnt signalling has also been reported in osteoblasts, in which the DNA-binding ability of TR3 is required for Wnt signalling repression 32. However, it remains unclear how TR3 individually regulates the components of Wnt signalling and thereby influences intestinal tumour progression.…”

Section: Introductionmentioning

confidence: 99%

The orphan receptor TR3 suppresses intestinal tumorigenesis in mice by downregulating Wnt signalling

Chen

et al. 2011

Gut

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Cross-talk between NR4A orphan nuclear receptors and β-catenin signaling pathway in osteoblasts

Cited by 27 publications

References 55 publications

The interplay of NR4A receptors and the oncogene–tumor suppressor networks in cancer

The interplay of NR4A receptors and the oncogene–tumor suppressor networks in cancer

Extracellular Purines Promote the Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells to the Osteogenic and Adipogenic Lineages

The orphan receptor TR3 suppresses intestinal tumorigenesis in mice by downregulating Wnt signalling

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